We examined the change in the correlation between glycated albumin (GA) and 2-hour postprandial plasma glucose (2 hPG) with increased urinary albumin. According to the albumin creatinine ratio (ACR), 222 noninsulin-dependent diabetic patients were divided into five groups: 69 patients with ACR less than 15 mg/g creatinine (Normo-A group), 35 patients with ACR between 15 and 30 mg/g creatinine (Normo-B group), 47 patients with ACR between 30 and 150 mg/g creatinine (Micro-A group), 30 patients with ACR between 150 and 300 mg/g creatinine (Micro-B group), and 41 patients with ACR greater than 300mg/g creatinine (Macro group). For these groups, the correlation between GA or HbA1c and 2 hPG sampled simultaneously or 1 month previously was examined. The correlation between GA and 2 hPG sampled simultaneously in the Micro-A group (r=0.741) was significantly stronger than that of the Normo-A group or the Macro group (r=0.536 and r=0.505, respectively) and that between HbA_1c and 2 hPG sampled simultaneously in the same group (r=0.499). These data showed that GA is a more useful indicator of glycemic control than HbAic in diabetic patients with microalbuminuria and ACR less than 150 mg/g creatinine.

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It is well-known that impaired nerve fiber regeneration is one of the major pathogens in diabetic neuropathy. In other hand, it has also been suggested that IL-6, one of the inflammatory cytokines, has an essential role in eliciting the nerve fiber regeneration.
We examined interleukin-6 (IL-6) levels and myelinated fiber regeneration in axotomized sciatic nerve in streptozotocin-induced diabetic rats. In non-axotomized nerve, using bioassay analysis, IL-6 was found to be expressed at low levels. However, a rapid but transient increase in IL-6 synthesis occurred in axotomized nerves, peak levels being reached less than three days after nerve injury. At 35 days after axotomy, myelinated fiber regeneration was quantitated using light microscopic morphometry. Regenerated fiber density was significantly reduced in a diabetic rat, to 32% of thatin a control, rat, and fiber size also decreased. Although both sections demonstrated some remnant of fiber degeneration, such as macrophage invasion and a destructive myelin, regeneration cluster was much more noticeable in the control rat.
The study we present here demonstrates decreased IL-6 synthesis in experimental diabetic neuropathy in vivo, but the mechanism of IL-6 suppression is still unknown. Further evaluation of the dynamics of recruited macrophage and functional deficits of Schwann cells on the nerve injury are required.

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First, profiles of sex hormone level and lipid metabolism in age-matched Japanese men with impaired glucose tolerance (IGT; n=22), non-insulin-dependent diabetes mellitus (NIDDM; n=36), ionships of the lipids and lipoprotein parameters to sex hormones, sex hormone-binding globulin (SHBG), insulin resistance (IR) score evaluated by HOMA model, estimated maximal oxygen uptake (VO2max), and abdominal fat accumulation were investigated in the 4 groups (C, IGT, NIDDM, and IGT+NIDDM). Body mass index (BMI) and waist-tohip ratio (WHR) in these patient groups increased significantly more than in the C group (p<0.05). The levels of the serum free testosterone (Free T) and high-density lipoprotein cholesterol (HDL-c) in the IGT and NIDDM groups were significantly lower than those in the C group (p<0.05). The level of SHBG in the NIDDM group was significantly lower than that in the C group. BMI, WHR, TC/HDL-c, LDL-c/HDL-c, FPG, FIRI, and IR score in the IGT+NIDDM group were significantly higher than those in the C group. On the other hand, HDL-c, free T, and SHBG levels in the IGT+NIDDM group were significantly lower than those in the C group. The IR score was elevated in the order NIDDM>IGT>C. Significant decreases in both Free T and SHBG levels in the patient groups were also observed after statistical adjustment for both BMI and WHR. A multiple regression analysis of lipid metabolism was performed for all 4 groups. In the C group, sex hormones and SHBG levels were not significantly associated with lipid and lipoprotein metabolism. In the IGT group, DHEA-s, total testosterone, and SHBG correlated siginificantly and independently with TC, HDL-c, and TG, respectively. In the NIDDM group, SHBG levels were significantly and independently associated with LDL-c/HDL-c. In the IGT+NIDDM group, total testosterone and VO2max were positively and independently related to HDL-c. Visceral fat area and SHBG were also independently related to TG. The IR score was independently associated with TC. VO₂max and SHBG were negatively and independently related to TC/HDL-c. VO₂max and IR score correlated independently with LDL/HDL-c. From these results, it was suggested that suppressed androgen and SHBG levels, and lipid abnormalities, may exist in patients with IGT and/or NIDDM, and insulin resistance, visceral fat accumulation, and endurance fitness, as well as lower levels of androgen and SHBG, were found to be independently related to lipid metabolism in the glucose-intolerant groups.

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Troglitazone is an oral hypoglycemic agent that reduces insulin resistance. Recent studies suggest that this agent is useful for the treatment of atherosclerosis, although the exact mechanism is unknown at present. Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, play important roles in the development of atherosclerosis. We therefore examined the relationship between troglitazone treatment and serum levels of adhesion molecules in diabetic patients. Twenty-seven patients with type 2 diabetes participated in this study. Seventeen patients were treated with troglitazone (400mg/day) and 10 patients with diet alone or a sulfonylurea drug (control group). Insulin sensitivity and serum concentrations of soluble adhesion molecules were measured before and 4 weeks after treatment. In the troglitazone group, insulin sensitivity, measured by the K index of the insulin tolerance test (KITT), significantly improved from 2.54±0.24 to 3.21±0.15%/min (p<0.05). Concentrations of soluble ICAM-1 significantly decreased from 197.6±18.7 to 168.4±11.1 ng/ml (p<0.05). Soluble E-selectin also significantly decreased from 70.2±8.3 to 57.8±6.2 ng/ml (p<0.05). However, soluble VCAM-1 was not altered by this treatment. Improvement of insulin sensitivity correlated inversely with changes in sE-selectin concentrations (r=-0.55, p<0.05). Contrarily, in the control group, no significant improvement in insulin sensitivity or decrement in soluble adhesion molecules were observed. Our results suggest that the anti-atherogenic effects of troglitazone are explained at least in part by reduced expression of adhesion molecules.

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[in Japanese]

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A hemoglobin specimen from a 46-year-old diabetic male was further analyzed because of an unexpectedly low HbA_1c value in comparison to the plasma glucose level and the presence of an abnormal peak on an ionexchange high performance liquid chromatography (HPLC) test was noted.
An additional band was observed between the HbA and HbA₂ bands on an isoelectrofocused polyacrylamide gel, suggesting the presence of a variant Hb. High-resolution ion-exchange HPLC using a Po1yCAT A, resin revealed the presence of an abnormal Hb and its glycated form. The glycation rate of the abnormal Hb was 10.4%, which is the same as that of normal HbA.This latter value was nearly equal to the immunoassay HbA_1c value. Electrospray ionization mass spectrometry revealed the presence of a variant β chain, which was 58 Da less than the normal structure. Analysis of the cleaved globin using on-line HPLC/ESI/MS/MS to determine the sequence revealed a new substitution [β 52 (D 3) Asp→Gly]. This substitution was ascertained using protein and DNA sequencer analysis. We designated this variant as “Hb Hokusetsu”
Hb Hokusetsu exhibits normal stability during isopropanol tests and has no significant difference in oxygen affinity or cooperativity.

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A 77-year-old male was admitted because of deterioration of liver function in December 1993. He had been diagnosed with non-insulin-dependent diabetes mellitus 8 years previously and had been treated with a daily subcutaneous injection of insulin for the past 4 years. He had also been diagnosed with chronic hepatitisC at the age of 72 years. One month after the start of daily intravenous injection of 80 mg of glycyrrhizin and subcutaneous injection of 26 units of human insulin, the patient experienced a hypoglycemic attack, and pseudoaldosteronism was observed. The glycyrrhizin and insulin doses were reduced, and the patient's blood glucose level and blood pressure became stable. When 80 mg of glycyrrhizin was injected again, it induced anotherhypoglycemic attack, in spite of lower dose of insulin. No hypoglycemic attacks occurred for the next five months, during which lower doses of glycyrrhizin were administered intermittently. The patient died of acute heart failure in August 1994. Autopsy showed chronic active hepatitis and diabetic nephropathy. Glycyrrhizin has various effects on the endocrine system and glycogen metabolism. The findings in this case suggested that glycyrrhizin should be carefully used in elderly patients and patients with diabetes mellitus and multiple organ impairment.

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We report 74-year-old male patient who had type 2 diabetes mellitus with the rare disease inclusion body myositis (IBM). The patient was diagnosed as having type 2 diabetes mellitus on 1979 (at 57 years of age). He was initially treated with an oral hypoglycemic agent, but his glycemic control gradually worsened. He began to notice muscle weakness in both legs in 1986. Although his glycemic control improved markedly after insulin administration, he was found to have elevated CK levels in 1994, and the elevated CK levels persisted along with exacerbated muscle weakness and atrophy in the legs. He was then rehospitalized on 1996 because of progressive muscle weakness of his legs, and the EMG findings, including denervation potentials, suggested diabetic amyotrophy. Because of the persistently elevated serum CK levels, a quadriceps muscle biopsy was performed. Histological examination of the muscle tissue showed advanced myopathic changes with inflammatory cellular infiltration, rimmed vacuoles and filamentous nuclear inclusions, which were the characteristic findings of IBM. Although the initial symptoms of IBM, including distal dominant muscle weakness, are similar to those of diabetic amyotrophy, their prognosis is very different, making the differential diagnosis of neuromusclar diabetic complications clinically important for patient follow-up.

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[in Japanese]

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